1. Field of Invention
This invention relates to the treatment of prostatic cancer and benign prostatic hypertrophy.
2. Description of Related Art
Conditional neoplasms are those that only grow to certain specific environmental conditions. Androgen-dependent neoplasms fall into such a category, being dependent upon a source of androgens to stimulate their proliferation. Without a source of androgens, they persist but do not proliferate. It is this rationale that supports the initial approach of orchidectomy in the treatment of prostatic cancer, withdrawing the principal source of androgens. Alternatively oestrogen therapy is as effective as orchidectomy, suppressing testicular activity and therefore androgen production by inhibiting the production of pituitary gonadotrophins. There is still some proliferation of prostatic neoplasms after orchidectomy or drug-induced castration, herein collectively referred to as "therapeutic castration", this being partly due to the androgens being secreted by the adrenal gland.
Endocrine therapy, either using androgen antagonists or synthetic oestrogens as described hereinafter, is commonly practised in the treatment of prostatic cancer, both in conjunction with, and independently of therapeutic castration. Oestrogen therapy can be used as described above in depressing testicular activity, and also to treat patients who have suffered a relapse after orchidectomy, as oestrogens have shown a direct regressive effect on the carcinomas of such relapsed patients.
The major drawback in oestrogen therapy is the increased incidence of fatal thromboembolitic disease. Nevertheless, some 60% of patients obtain some relief with diethylstilboestrol, a synthetic oestrogen, a third of whom become refractory and die within two years. Flutemide and cyproterone acetate are two non-steroidal compounds that antagonize androgens; this property also offsets the feedback of androgens in the hypothalamus, stimulating an increase in the levels of luteinzing hormone (LH). The compounds are therefore not appropriate for use in non-castrate patients. Aminoglutethimide (AG) has been tried in the treatment of prostatic cancer as it blocks the side chain cleavage of cholesterol by inhibiting the enzyme desmolase. The results in a reduction of androgens, oestrogens and cortisol. A wide range of trials have been performed, the results of which indicate that some benefit s derived from the use of AG in orchidectomized patients in relapse (Chang A.Y. et al. Am. J. Clan. Oncol. 12 (4) 358-60 (1989)). The use of AG has been combined with hydrocortisone (as a cortisol replacement) but side effects such as skin rashes, lethargy and thrombocytopenia have still been observed (Elomaa I. et al. Eur. Urol. 14 (2) 104-6 (1988)). The actual mechanism through which AG is effective in the treatment of prostatic cancer is debated. Dowsett M. et al. (Br. J. Cancer 57 (2) 190-2 (1988)) do not attribute it to a lowering of adrenal androgen secretion, whereas others in this field do. Overall, the need for cortisol replacement therapy and the undesirable side effects limit the use of AG in treating prostatic cancer.
Additional prior art is referred to in a separate section after "Summary of the Invention", without which its context would not be clear.